In this session, Blanca Rodríguez Estrada, Genetics Lab Manager at iGLS, in-house Reproductive Genetics Laboratory of the IVF Life Group, talked about the NIPT test, what is for and how accurate the results are.
This is a limitation of the SNPs (“snips”) based NIPT uses the maternal profile and the paternal profile to compare them as we know, the fetus would have a combination of maternal, and paternal profile. In this case, the maternal genetic load will be the egg donor’s genetic load, so it would be possible, but it’s a tricky field because we will have 3 different sources of DNA in the maternal’s blood. We will have the DNA from the maternal’s blood cells itself, and fatal DNA that will have half of its paternal pattern and half of the egg donor’s pattern. Theoretically, it can be done, but it’s a limitation of the snip based NIPT. It can be always done with NGS-based NIPT.
It is mainly because the conditions due to sex chromosomes are less common in the population than those two other chromosomes. Sensitivity is calculated by the percentage of positives that are real positives. When we have a lot of positives that can be confirmed by an invasive procedure, we have a high sensitivity.
That is why the sensitivity is lower than with other trisomies such as 21, which causes down syndrome. Down syndrome is really common within other aneuploidies. We don’t have many sex chromosome aneuploidies. When we tried to do a theoretical sensitivity calculation, it had been higher than the real one because the real one is based on the actual cases we have. We don’t have that many cases, so that’s why it is slower than the sensitivity of other chromosomes.
When using NGS, you can check every chromosome, such as 13, 18 and 21, which causes the most common aneuploidies related to autosomes, but you can also check the sex chromosomes. As I said, the sensitivity for each chromosome will vary because the sex chromosomes are not that common, but every chromosome can be checked.
That’s a tricky question, it’s difficult to know the quantity, we can’t say how many cells have suffered from lysis or have extracted the DNA, and they are the cell-free DNA we need. We can calculate is how much fatal fraction we need in the blood, and for the baby’s safety, it’s a 3.5% of fetal fraction. Also, cell-free DNA can be detected after five weeks of pregnancy, if I’m not wrong. It can be detected, but until the 9th week of pregnancy, we can’t calculate if we are having aneuploidy on the embryo or the differences in each chromosome are due to a low fetal fraction.
The test can check the sexual chromosome, but the gender will be only revealed if the patient wants to know. We can test the sex chromosome and tell the patient that they are normal or abnormal. If the patient doesn’t want to know the gender, we cannot reveal it. We know the gender of the fetus because the mother is always XX, and so if we don’t have any copy of the Y chromosome, we assume that we are having a female XX, and if we have one copy of the Y chromosome, we assume that we are having a male XY.
When we are having twin pregnancies, it’s difficult to distinguish if the two of the fetus are males. When we have a Y copy, we can say that we have at least one male, but we cannot distinguish the second one, we cannot say if both of them are males or if you have one male and one female.
Yes, as I said, it’s possible, if you have a twin pregnancy or in your family, you have a twin brother, I would recommend looking for NIPT that uses NGS technologies because NGS is prepared for this kind of situations where we have a third source of DNA material. As I said, it’s possible, and the only tricky part is that we cannot distinguish the sex. Also, if we have a high risk on any of the chromosomes, even the sexual ones, we cannot distinguish, which of the fetus is the one that is affected, but you can do NIPT for sure.
I don’t know the numbers for the detection of XXY, so having two copies of the X chromosome and one copy of the Y chromosome. I don’t have the numbers, but as I said, the sensitivity of the test is high for the sex chromosomes, and the sensitivity is a bit lower than the ultrasounds, but it’s high. If you had more than 83% of the aneuploidies detected by NIPT, we can extrapolate that 83% (which is not a real number) of the XXY may be confirmed by an invasive procedure based on the data of the sex chromosomes.
NIPT can be wrong, but it happens very rarely. It can be comparable to invasive procedures because the positive predictive value is high, it’s 99.9%, which is even the maximum, but it always has to be confirmed by an invasive procedure. This is because we cannot separate the DNA coming from the mother and the DNA coming from the fetus.
We are doing maths calculations to know if the fetus has an aneuploidy or has a high risk of having an aneuploidy, and we must talk in these terms of the risk of having aneuploidies. As I said, every high-risk result on NIPT has to be confirmed, and that doesn’t mean that NIPT has a high positive predictive value, and I would recommend doing it before an invasive procedure.
I think the Harmony test is a commercial name for a NIPT, which is the technique.
The snip is a Single-Nucleotide Polymorphism. In the DNA, we have a pair of bases that are named after letters: A, T, G, and C, normally, we have a sequence of these letters that are common in all humans, but sometimes in certain points of the DNA, we have changes that don’t affect our life, our development but are marking every individual.
I have certain letters of my DNA that are different from yours and my sister’s. These snips, these bases that are changed, can be used to create patterns that are different in every individual, this is used, for example, for fingerprinting. This is a really useful tool to find out if your DNA is actually from the mother or is a mix of the mother and the father.
It’s not more reliable, I think the reason for not waiting too much, it’s more based on not making the patient wait for the result. If you have passed the ninth week of pregnancy and still want to do NIPT, you can do it. You can also do a NIP if you are next to your delivery, but the reason why, and we are trying to do the screening earlier, even in the first trimester, is that we want to reduce the time of waiting for our first information about the fetus, so of course, you can do a NIPT any time during your pregnancy, and the result will not vary.
It is having been set up for the first trimester, but you can do it even after it. However, I don’t see the point of doing it after the first, the second trimester, where you have been doing echography, ultrasound, so maybe you have more information. If you go for a NIPT because your clinician has seen an abnormality in echography or an abnormal liver, level of hormones, of course, go for it.
If you have a normal pregnancy and are in your second or even third trimester, I don’t see the point of doing it and waiting that long. I would recommend doing it in the first semester.